Abstract

BACKGROUND:

There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure.

RESULTS:

In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m³, 4 hours/day, 10 days, 5 ± 2 nm primary size). Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma-optical emission spectroscopy (ICP-OES) was 31 μg/g lung (dry weight) immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu.

CONCLUSIONS:

Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

SEM-EDS mapping of nanosilver aerosols deposited on TEM grid during the exposure. The colored dots represent the elemental map for Ag at the expected characteristic X-ray energy for Ag and show, based on size, the presence of silver nanoparticle agglomerates.

Results from analysis of BAL fluid after sub-acute exposure to Ag nanoparticles (n = 5 per each group). Data from Ref. 34 for Cu nanoparticle exposure (n = 6 per control group, n = 8 per Cu-exposed group) using the same protocol are shown for comparison. Number and percentages of differential cells in BAL, * p < 0.05 and ** p < 0.01 (A). Percent change from control animals in total cells, total protein and activity of LDH (B). Data are expressed as mean ± SE.